Genome-wide association study of Alzheimer's disease with psychotic symptoms

Psychotic symptoms occur in ~40% of subjects with Alzheimer's disease (AD) and are associated with more rapid cognitive decline and increased functional deficits. They show heritability up to 61% and have been proposed as a marker for a disease subtype suitable for gene mapping efforts. We undertook a combined analysis of three genome-wide association studies (GWASs) to identify loci that (1) increase susceptibility to an AD and subsequent psychotic symptoms; or (2) modify risk of psychotic symptoms in the presence of neurodegeneration caused by AD. In all, 1299 AD cases with psychosis (AD+P), 735 AD cases without psychosis (AD-P) and 5659 controls were drawn from Genetic and Environmental Risk in AD Consortium 1 (GERAD1), the National Institute on Aging Late-Onset Alzheimer's Disease (NIA-LOAD) family study and the University of Pittsburgh Alzheimer Disease Research Center (ADRC) GWASs. Unobserved genotypes were imputed to provide data on >1.8 million single-nucleotide polymorphisms (SNPs). Analyses in each data set were completed comparing (1) AD+P to AD-P cases, and (2) AD+P cases with controls (GERAD1, ADRC only). Aside from the apolipoprotein E (APOE) locus, the strongest evidence for association was observed in an intergenic region on chromosome 4 (rs753129; 'AD+PvAD-P' P=2.85 × 10(-7); 'AD+PvControls' P=1.11 × 10(-4)). SNPs upstream of SLC2A9 (rs6834555, P=3.0 × 10(-7)) and within VSNL1 (rs4038131, P=5.9 × 10(-7)) showed strongest evidence for association with AD+P when compared with controls. These findings warrant further investigation in larger, appropriately powered samples in which the presence of psychotic symptoms in AD has been well characterized.Molecular Psychiatry advance online publication, 18 October 2011; doi:10.1038/mp.2011.125.

The canadian longitudinal study on aging (CLSA)

Canadians are living longer, and older persons are making up a larger share of the population (14% in 2006, projected to rise to 20% by 2021). The Canadian Longitudinal Study on Aging (CLSA) is a national longitudinal study of adult development and aging that will recruit 50,000 Canadians aged 45 to 85 years of age and follow them for at least 20 years. All participants will provide a common set of information concerning many aspects of health and aging, and 30,000 will undergo an additional in-depth examination coupled with the donation of biological specimens (blood and urine). The CLSA will become a rich data source for the study of the complex interrelationship among the biological, physical, psychosocial, and societal factors that affect healthy aging. © 2009 Canadian Association on Gerontology.

Management of Hyperphosphataemia in Chronic Kidney Disease:Summary of National Institute for Health and Clinical Excellence (NICE) Guideline

Bone disease and ectopic calcification are the two main consequences of hyperphosphataemia of chronic kidney disease (CKD). Observational studies have demonstrated that hyperphosphataemia in CKD is associated with increased mortality. Furthermore, the use of phosphate binders in dialysis patients is associated with significantly lower mortality. The UK Renal Registry data show significant underachievement of phosphate targets in dialysis patients. It is believed to be due to wide variation in how management interventions are used. The National Institute for Health and Clinical Excellence (NICE) has developed a guideline on the management of hyperphosphataemia in CKD. This is based on the evidence currently available using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. This review outlines the recommendations including research recommendations and discusses methodology, rationale and challenges faced in developing this guideline and the health economic model used to assess the cost-effectiveness of different phosphate binders. © 2013 S. Karger AG, Basel.

The Effect of Health and Penal Harm on Aging Female Prisoners' Views of Dying in Prison

With tougher sentencing laws, an increasing number of individuals are finding themselves spending their final years in life in prison. Drawing on a sample of 327 women over the age of 50 incarcerated in 5 Southern states, the present study investigates the relationship between numerous health variables and the Templer Death Anxiety Scale (TDAS). Qualitatively, the article also provides personal accounts from inmates that serve to reinforce death fears when engaging the prison health care system. Participants reported a mean of 6.40 on the TDAS indicating a substantial degree of death and anxiety when compared to community samples. both mental and physical health measures were important indicators of death anxiety. Qualitative information discovered that respondents' concerns about dying in prison were often influenced by the perceived lack of adequate health care and the indifference of prison staff and other instances of penal harm.

UK National Report on Asylum and the Status of Non-EU Aliens

(with G. Anthony)

Speaking with One Voice?: Ethno-national Division on the Constitutional Court of Bosnia-Herzegovina

The challenge of designing institutions to manage ethno-national conflict is one of the enduring concerns of political science. One important but relatively understudied aspect of this challenge is the design of constitutional courts. Courts are likely to play a key role in the maintenence of a constitutional settlement. But this role can be especially onerous in a deeply divided and post-conflict setting where the rule of law is weak and judges have ethno-national affiliations that may undermine the appearance of judicial neutrality. In such contexts, a court’s authority (including compliance with its decisions) cannot be taken for granted.

With reference the Constitutional Court of Bosnia-Herzegovina, and using an original dataset of the Court's non-unanimous plenary decisions, we test several hypotheses about the degree to which ethno-national affiliation influences judicial behavior. We find that (1) judges on the Constitutional Court do in fact divide predictably along ethno-national lines, (2) that these patterns are robust to changes in the tenure system, and (3) are independent of party political background.

The Role and Effectiveness of Public – Private Partnerships (NHS LIFT) in the Development of Enhanced Primary Care Premises and Services:Report for the National Institute for Health Research Service Delivery and Organisation programme

The research project analysed the role and effectiveness of LIFT via a multi-method study which included semi-structured interviews with policy elites and users, as well as case studies and an exploratory analysis of the financial characteristics of three LIFT Companies. While the team felt that it was able to identify key aspects relating to the advantages and drawbacks surrounding LIFT, some aspects relating to the representativeness of the study was adversely affected by a reluctance of PCTs to participate in the case study analysis and commercial confidentiality restrictions. The study was nonetheless able to identify important issues in relation to the funding and procurement of primary care premises and services.

Perceptions of aging across 26 cultures and their culture-level associates

College students (N = 3,435) in 26 cultures reported their perceptions of age-related changes in physical, cognitive, and socioemotional areas of functioning and rated societal views of aging within their culture. There was widespread cross-cultural consensus regarding the expected direction of aging trajectories with (a) perceived declines in societal views of aging, physical attractiveness, the ability to perform everyday tasks, and new learning; (b) perceived increases in wisdom, knowledge, and received respect; and (c) perceived stability in family authority and life satisfaction. Cross-cultural variations in aging perceptions were associated with culture-level indicators of population aging, education levels, values, and national character stereotypes. These associations were stronger for societal views on aging and perceptions of socioemotional changes than for perceptions of physical and cognitive changes. A consideration of culture-level variables also suggested that previously reported differences in aging perceptions between Asian and Western countries may be related to differences in population structure.

PAlliative Care in chronic Kidney diSease: the PACKS study—quality of life, decision making, costs and impact on carers in people managed without dialysis

BACKGROUND: The number of patients with advanced chronic kidney disease opting for conservative management rather than dialysis is unknown but likely to be growing as increasingly frail patients with advanced renal disease present to renal services. Conservative kidney management includes ongoing medical input and support from a multidisciplinary team. There is limited evidence concerning patient and carer experience of this choice. This study will explore quality of life, symptoms, cognition, frailty, performance decision making, costs and impact on carers in people with advanced chronic kidney disease managed without dialysis and is funded by the National Institute of Health Research in the UK.

METHODS: In this prospective, multicentre, longitudinal study, patients will be recruited in the UK, by renal research nurses, once they have made the decision not to embark on dialysis. Carers will be asked to 'opt-in' with consent from patients. The approach includes longitudinal quantitative surveys of quality of life, symptoms, decision making and costs for patients and quality of life and costs for carers, with questionnaires administered quarterly over 12 months. Additionally, the decision making process will be explored via qualitative interviews with renal physicians/clinical nurse specialists.

DISCUSSION: The study is designed to capture patient and carer profiles when conservative kidney management is implemented, and understand trajectories of care-receiving and care-giving with the aim of optimising palliative care for this population. It will explore the interactions that lead to clinical care decisions and the impact of these decisions on informal carers with the intention of improving clinical outcomes for patients and the experiences of care givers.

Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU):A randomised, double-blind, placebo-controlled trial

Background: Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or coma. Methods: We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2·5 mg or 0·9% saline placebo intravenously every 8 h, irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days of treatment, whichever came first. Delirium was assessed using the confusion assessment method for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14 day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. Findings: 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p=0·53). The most common adverse events were oversedation (11 patients in the haloperidol group vs six in the placebo group) and QTc prolongation (seven patients in the haloperidol group vs six in the placebo group). No patient had a serious adverse event related to the study drug. Interpretation: These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients. Although haloperidol can be used safely in this population of patients, pending the results of trials in progress, the use of intravenous haloperidol should be reserved for short-term management of acute agitation. Funding: National Institute for Health Research. © 2013 Elsevier Ltd.